Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+cohort in EGF103009, a phase II study
Lapatinib monotherapy in patients with HER2-overexpressing relapsed or refractory inflammatory breast cancer: final results and survival of the expanded HER2+cohort in EGF103009, a phase II study
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DOI：
10.1016/s1470-2045(09)70087-7
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发表时间：
2009-06-01
期刊：
影响因子：
51.1
通讯作者：
Johnston, Stephen
中科院分区：
文献类型：
--
作者：
Kaufman, Bella;Trudeau, Maureen;Johnston, Stephen
背景 炎性乳腺癌是一种侵袭性且生物学上独特的形式，与其他乳腺癌相比，HER2 过度表达的频率更高。对于对传统蒽环类药物或紫杉烷类药物和曲妥珠单抗治疗耐药的患者，选择是有限的。拉帕替尼是一种口服可逆性表皮生长因子受体酪氨酸激酶抑制剂，此前在 30 名 HER2 过表达 (HER2+) 复发性或蒽环类难治性炎性乳腺癌患者的队列中，有 50% 的缓解率。我们的目的是评估拉帕替尼在扩大的复发或难治性 HER2+ 疾病患者队列中的疗效。 方法 从 2005 年 3 月到 2007 年 9 月，在一项非随机、开放标签、11 期研究中，126 名复发或难治性 HER2+ 炎性乳腺癌患者接受拉帕替尼 1500 mg 每日一次治疗。进行治疗前肿瘤活检以验证炎性乳腺癌的病理特征。每 4 周评估一次皮肤病，每 8 周通过实体瘤 (RECIST) 标准的反应评估来评估可测量的局部晚期或转移性疾病部位的反应。主要目的是通过临床可评估的皮肤病标准和 RECIST（如果适用）评估综合客观缓解率。分析是按意向治疗进行的；数据缺失的患者被视为无反应。这项研究已在 ClinicalTrials.gov 注册，编号为 NCT00105950。结果临床表现和生物标志物分析显示肿瘤分子特征与炎性乳腺癌一致。没有患者获得完全缓解。 49 名患者（39%；95% CI 30-48）有部分缓解。中位无进展生存期为 14.6 周 (95% Cl 12.1-16.0)，中位缓解持续时间为 20.9 周 (12.7-32.1)。对拉帕替尼产生反应的可能性不受之前曲妥珠单抗治疗的影响。 141 名患者中有 130 名 (92%) 发生至少一种不良事件； 45 名患者 (32%) 出现严重不良事件，最常见的是呼吸困难（8 名患者）和胸腔积液（6 名患者）。 5 名患者出现了可能与治疗相关的致命不良事件。 解释 拉帕替尼单药疗法是治疗复发性或难治性 HER2+ 炎性乳腺癌的潜在有效疗法。
Background Inflammatory breast cancer is an aggressive and biologically distinct form with a higher frequency of HER2 overexpression than other breast cancers. For patients with resistance to conventional anthracycline or taxane and trastuzumab treatment, options are limited. Lapatinib, an oral reversible inhibitor of epidermal growth factor receptor tyrosine kinases, previously had a 50% response rate in a cohort of 30 patients with HER2-overexpressing (HER2+) recurrent or anthracycline-refractory inflammatory breast cancer. We aimed to assess efficacy of lapatinib in an expanded cohort of patients with relapsed or refractory HER2+ disease.Methods From March, 2005, to September, 2007, 126 patients with relapsed or refractory HER2+ inflammatory breast cancer were treated with lapatinib 1500 mg once daily in a non-randomised, open-label, phase 11 study. Pretreatment tumour biopsies were done to verify pathological features of inflammatory breast cancer. Skin disease was assessed every 4 weeks, and response in sites of measurable locally advanced or metastatic disease were assessed by response evaluation in solid tumours (RECIST) criteria every 8 weeks. The primary aim was to assess combined objective response rate, by clinically evaluable skin disease criteria and RECIST, if applicable. Analyses were done by intention to treat; patients with missing data were treated as non-responders. This study is registered with ClinicalTrials.gov, number NCT00105950.Findings Clinical presentation and biomarker analysis showed a tumour molecular profile consistent with inflammatory breast cancer. No patients had complete response. 49 patients (39%; 95% CI 30-48) had partial response. Median progression-free survival was 14.6 weeks (95% Cl 12.1-16.0), with median duration of response of 20.9 weeks (12.7-32.1). Likelihood of response to lapatinib was not affected by previous treatment with trastuzumab. 130 (92%) of 141 patients had at least one adverse event; 45 (32%) had serious adverse events, the most common were dyspnoea (eight patients) and pleural effusion (six). Five patients had fatal adverse events that were possibly treatment related.Interpretation Lapatinib monotherapy is a potentially effective treatment for relapsed or refractory HER2+ inflammatory breast cancer.